Cell Reports (Jun 2024)
Immunotherapeutic targeting of surfaceome heterogeneity in AML
- Marie-Eve Bordeleau,
- Éric Audemard,
- Arnaud Métois,
- Louis Theret,
- Véronique Lisi,
- Azer Farah,
- Jean-François Spinella,
- Jalila Chagraoui,
- Ossama Moujaber,
- Léo Aubert,
- Banafsheh Khakipoor,
- Laure Mallinger,
- Isabel Boivin,
- Nadine Mayotte,
- Azadeh Hajmirza,
- Éric Bonneil,
- François Béliveau,
- Sybille Pfammatter,
- Albert Feghaly,
- Geneviève Boucher,
- Patrick Gendron,
- Pierre Thibault,
- Frédéric Barabé,
- Sébastien Lemieux,
- Guillaume Richard-Carpentier,
- Josée Hébert,
- Vincent-Philippe Lavallée,
- Philippe P. Roux,
- Guy Sauvageau
Affiliations
- Marie-Eve Bordeleau
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Corresponding author
- Éric Audemard
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Arnaud Métois
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Louis Theret
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Véronique Lisi
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada
- Azer Farah
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada
- Jean-François Spinella
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Jalila Chagraoui
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Ossama Moujaber
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Léo Aubert
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Banafsheh Khakipoor
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada
- Laure Mallinger
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Isabel Boivin
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Nadine Mayotte
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Azadeh Hajmirza
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Éric Bonneil
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- François Béliveau
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Quebec Leukemia Cell Bank, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, Canada
- Sybille Pfammatter
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Albert Feghaly
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Geneviève Boucher
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Patrick Gendron
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Pierre Thibault
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Department of Chemistry, Faculty of Arts and Science, Université de Montréal, Montréal, QC H3T 1J4, Canada
- Frédéric Barabé
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, Québec, QC G1V 4G2, Canada
- Sébastien Lemieux
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Corresponding author
- Guillaume Richard-Carpentier
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada; Department of Medicine, Division of Medical Oncology and Hematology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Corresponding author
- Josée Hébert
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Quebec Leukemia Cell Bank, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, Canada; Corresponding author
- Vincent-Philippe Lavallée
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Centre Hospitalier Universitaire Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada; Department of Pediatrics, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Hematology and Oncology Division, Centre Hospitalier Universitaire Sainte-Justine, Montréal, QC H3T 1C5, Canada; Corresponding author
- Philippe P. Roux
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Corresponding author
- Guy Sauvageau
- The Leucegene project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada; Quebec Leukemia Cell Bank, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, Canada; Corresponding author
- Journal volume & issue
-
Vol. 43,
no. 6
p. 114260
Abstract
Summary: Immunotherapy remains underexploited in acute myeloid leukemia (AML) compared to other hematological malignancies. Currently, gemtuzumab ozogamicin is the only therapeutic antibody approved for this disease. Here, to identify potential targets for immunotherapeutic intervention, we analyze the surface proteome of 100 genetically diverse primary human AML specimens for the identification of cell surface proteins and conduct single-cell transcriptome analyses on a subset of these specimens to assess antigen expression at the sub-population level. Through this comprehensive effort, we successfully identify numerous antigens and markers preferentially expressed by primitive AML cells. Many identified antigens are targeted by therapeutic antibodies currently under clinical evaluation for various cancer types, highlighting the potential therapeutic value of the approach. Importantly, this initiative uncovers AML heterogeneity at the surfaceome level, identifies several antigens and potential primitive cell markers characterizing AML subgroups, and positions immunotherapy as a promising approach to target AML subgroup specificities.
